Ischemia In Isolated Rat Heart Research Articles

Ischaemic contracture in isolated rat heart: reversible or irreversible myocardial injury?

An isolated rat heart preparation was reperfused at 37 degrees C for 10 min after 10, 20, 30 and 40 min of ischaemia. The left ventricular tension was measured by means of a balloon catheter filled with water and connected to a pressure recorder. The left ventricular resting tension began to increase at 9 +/- 1 min (mean +/- SEM) and was maximally developed (myocardial contracture) at 18 +/- 1 min of ischaemia. There was a striking and constant exacerbation of the resting tension during reperfusion after 30 and 40 min (but not after 10 or 20 min) of ischaemia with simultaneous acceleration of creatine phosphokinase (CK) release into the coronary effluent and with the loss of the recovery of contractile activity. Myocardial adenosine triphosphate (ATP)-content decreased during 20 min of ischaemia more in the endocardial (ENDO) (from 17.7 +/- 1.9 mumol/g to 0.7 +/- 0.1 mumol/g) than in epicardial (EPI) (from 15.5 +/- 0.9 mumol/g to 3.2 +/- 0.6 mumol/g) parts of myocardium. Reperfusion after 10 min of ischaemia resulted in a slight increase of myocardial ATP-content both in EPI (from 7.5 +/- 0.6 to 10.4 +/- 0.8 mumol/g, p less than 0.05) and ENDO (from 5.0 +/- 0.8 to 8.9 +/- 2.5 mumol/g, n.s.). Reperfusion after the completion of contracture (after 20 min) had no effect on myocardial ATP-content. The results indicate that there is a transmural ATP gradient in ischaemic isolated rat heart and that myocardial ATP net production during reperfusion (10 min) is prevented after the development of ischaemic contracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct Effects of Streptokinase on the Isolated Rat Myocardium

The utilization of streptokinase as a thrombolytic agent is prevalent in the management of patients following a myocardial infarction. The present investigation was designed to assess the direct effects of streptokinase infusion on the normal isolated rat heart and on the globally ischemic isolated rat heart. The effects of streptokinase on the mechanical function of the hearts were monitored, as well as the effects on the membrane integrity of the cells, as indicated by enzyme release. The normal hearts were infused with either buffer or streptokinase. Both the normal and streptokinase-treated normal hearts exhibited a decrease in function during the course of each experiment. Under these conditions, there were no significant differences in the values for mechanical function in either group. The release of lactate dehydrogenase (LDH) and creatine kinase (CK) into the coronary effluents was not significantly increased during the infusion of streptokinase. There was a significant increase in the release of nucleosides during the streptokinase infusion period compared with the buffer infusion period. The infusion of either buffer or streptokinase was compared in the preischemic and postischemic rat heart. The values obtained during preischemic infusion with buffer or streptokinase were comparable to the values obtained in the normal and streptokinase-treated normal hearts. There were no significant differences in the values for mechanical function measured during buffer infusion following ischemia compared with those measured during streptokinase infusion following ischemia. In the postischemic hearts, there was a sixfold increase in the release of nucleosides during buffer infusion, whereas only a twofold increase was observed in the postischemic hearts during streptokinase infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracellular calcium and electrogram in ischemic isolated rat heart.

The electrogram (EG) of the isolated rat heart during ischemic or anoxic perfusion has been studied. Reduction of the coronary flow rate (CFR) induced an increase of voltage (V) both in unipolar epicardial EG and in transmural bipolar EG. The V increase did not occur during anoxic perfusin. The ischemic increase cannot be due to a disturbance in the His-Purkinje or intraventricular conduction because it was observed also in the circumscribed myocardial area, which was explored by means of the transmural bipolar EG. Likewise it cannot be due to an intramural block because it occurs before one observes an augmentation of epicardial activation time or a decrease of dV/dtmax. Therefore, the ischemic V increase should be due to a modification of transmembrane potential. The variation rate of V, of dP/dt, and of myocardial ATP behaved in a similar way during underperfusion. Varying intracellular Ca2+ by means of a Ca2+-free medium or verapamil reduces the ischemic V increase. The dynamics of the ischemic V increase may be represented in order of succession by: inhibition of oxidative metabolism, augmentation of intracellular Ca2+, increase of K+ conductance, and hyperpolarization of cardiac cells.

Protection of mitochondrial function during ischemia by potassium cardioplegia: correlation with ischemic contracture.

The effect of potassium cardioplegia on mitochondrial function was evaluated in the ischemic isolated rat heart. Mitochondrial function as well as adenosine triphosphate (ATP) levels were determined at the initiation of ischemic contracture, at the completion of ischemic contracture, and 20 minutes following contracture completion. Group I received no cardioplegia prior to ischemia, while Group II received potassium cardioplegia prior to the onset of ischemia. The respiratory control index (RCI), which is the primary measure of the intactness of mitochondrial function, was calculated with both a NAD (nicotinamide adenine dinucleotide)-linked substrate and a FAD (flavin adenine dinucleotide)-linked substrate. Potassium cardioplegia significantly delayed ischemic contracture initiation and completion. Although the RCI and ATP levels decreased significantly at successive levels of contracture, there was no difference in the RCI or ATP content between Group I and Group II at contracture initiation or completion. Unlike previous investigations that have used a time-base to examine mitochondrial function and acute cardiac ischemic injury, we correlated mitochondrial function with the measurable physiologic event ischemic contracture. The data indicated that potassium cardioplegia preserved ATP content and mitochondrial function, and that contracture initiation and completion correlate well with specific ATP levels and mitochondrial respiratory control. The relationship between mitochondrial function and ATP content indicates that the beneficial effect of potassium cardioplegia on mitochondrial function may be secondary to the preservation of high-energy phosphate levels which provide energy for mitochondrial maintenance.

Significance of enzyme release from ischemic isolated rat heart.

Whole-heart ischemia has been induced in isolated working rat heart. The distribution of the reduced coronary flow was even, as judged by 3H-antipyrine autoradiographs. Reducing the coronary flow resulted in myocardial ischemia, as indicated by a lowered tissue content of glycogen, ATP and creatine phosphate and accumulation of lactate. After a reperfusion period of 30 min there was a restoration of glycogen, ATP and creatine phosphate for hearts that were ischemic for 5 and 10 min, with a concomitant normalization of tissue lactate. Hearts that were ischemic for 30 min did not show restoration of high energy phosphates and glycogen. There was a leakage of ASAT, CK and LD in all groups of hearts, suggesting that a release of these enzymes does not necessarily indicate an irreversibly damaged myocardial cell.

The mechanism of myocardial protection from ischemic arrest by intracoronary tetrodotoxin administration

Intracoronary injection of 14 mcg. of tetrodotoxin into the ischemic isolated rat heart resulted in immediate cessation of mechanical activity. Upon reperfusion with oxygenated, modified Krebs-Henseleit bicarbonate buffer in a modified Langendorff apparatus, all hearts recovered normal rate, rtythm, and contractile vigor after up to 60 minutes of ischemia. In contrast, all hearts not administered tetrodotoxin showed bradycardia, irregular rhythm, and weak contraction upon reperfusion after 30 and 45 minutes of ischemia; after 60 minutes, no mechanical activity was evident. The improved cardiac function following ischemia in the tetrodotoxin-treated hearts was associated with persistence of normal adenosine triphosphate (ATP) levels after up to 30 minutes of ischemia and normal or elevated creatine phosphate (CP) levels after up to 60 minutes of ischemia. On the other hand, ATP and CP levels progressively declined to reach 50 per cent of normal values after 30 minutes in the ischemic hearts without tetrodotoxin. These findings indicate that postarrest ATP and CP levels play an important role in myocardial recovery after ischemic arrest.